Your DNA can influence how drugs work on you as an individual. In the same way some people are tall and some are short, some people metabolize drugs differently. On this episode of the Healthcare Triage podcast, Aaron talks to Dr. Todd Skaar, who leads the IU Precision Health Initiative Pharmacogenomics program. You'll learn about his research into how genes we inherit from our parents can impact the way we respond to drugs.
This episode of the Healthcare Triage podcast is sponsored by Indiana University School of Medicine whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research and patient care.
IU School of Medicine is leading Indiana University's first grand challenge, the Precision Health Initiative, with bold goals to cure multiple myeloma, triple negative breast cancer and childhood sarcoma and prevent type 2 diabetes and Alzheimer's disease
Dr. Aaron Carroll: Hi. Welcome back to the Healthcare Triage podcast. Today's guest is Todd Skaar, He's a professor of medicine and leader of the pharmacogenomics program associated with the Precision Health Initiative at Indiana University School of Medicine. Todd, welcome to the show.
Dr. Todd Skaar: Thank you.
Dr. Aaron Carroll: This Healthcare Triage podcast is sponsored by Indiana University School of Medicine, whose mission is to advance health in the State of Indiana and beyond, by promoting innovation and excellence in education, research and patient care. IU School of Medicine is leading Indiana University's first grand challenge, the Precision Health Initiative with bold goals to cure multiple myeloma, triple negative breast cancer and childhoods or coma, and prevent type two diabetes and Alzheimer's disease. If we could just start by you introducing yourself and telling us what position you have at IU and what you do?
Dr. Todd Skaar: Yeah. So my name is Todd Skaar. I'm a Professor of Medicine in the department of medicine and in the division of clinical pharmacology. And I'm the leader of the pharmacogenomics program for the Precision Health Initiative here at IU School of Medicine.
Dr. Aaron Carroll: So we often like to talk to our guests about how did you get to where you are and sort of, how did you get interested in this field to begin with?
Dr. Todd Skaar: When I was doing my post-doc at Georgetown University at the Lombardi Cancer Center there, and I was on faculty for a while. This was back around 2000, 2001, and I started realizing that there was a lot of inter-individual variability in the way people responded to drugs. And it was things that we having a hard time solving, that sort of stuff in cell culture and Petri dishes and cells.
And there was an opportunity to come here to Indiana University, where they're really focusing on pharmacogenomics and trying to understand how the genes that we inherit from our parents really impact the way we respond to drugs. And so I saw that as an opportunity and that was really early stages back then, and then we've been working on developing it since then.
Dr. Aaron Carroll: So what is pharmacogenomics?
Dr. Todd Skaar: That's really trying to understand how our genetics... So how the genes that we inherit from our parents, how that really impacts the way we respond to drugs. A lot of people respond differently to drugs. Some people might say, "Oh yeah, this drug works good for me," and a different person may say, "Well, I just get side effects from that."
And part of that is due to environment, could be what we eat, the way we grew up, all kinds of different things. But part of it is also a factor of the genes that we inherited from our parents and how that impacts the way we respond to drugs. And thus, the pharmaco is the drugs and genomics is the genes.
Dr. Aaron Carroll: So is this like all drugs, certain drugs or something in between?
Dr. Todd Skaar: I would say more certain drugs at this point, that we know of. There probably is some genetic component to all drugs, but at this point, the ones that we're really focused on is a limited number of a dozen or so that we really have really good evidence, that we know how our genetics impact the response.
Dr. Aaron Carroll: Well, that was my next question, is how does that actually operationalize? Why would our genetics influence how well drugs work?
Dr. Todd Skaar: So there's a couple different ways. One that we call pharmacokinetics and what that is, is the way our body handles drugs after we take them. So you take a pill, it gets absorbed into your blood. And then in most cases, your liver is one of the main organs that gets rid of it for you. You don't want it hanging around in your body forever, and your liver sees it as something to get rid of and it gets rid of it.
There's some enzymes, some proteins in the liver that are responsible for getting rid of these drugs. And what we actually have found out is that the genes that encode those enzymes, that we have inherited from our parents, some of us have differences in our genes to the extent that they don't work on certain drugs, whereas other people's do. It's part of this understanding whether your body is able to rapidly get rid of a drug, or whether the drug hangs around in your body for a long time.
So that's the part that relates to how our body handles the drug. And then there's the other part, which is a pharmacodynamics, which is the targets of the drug and what the drug actually does to our body. And there's genetic, all of those things are encoded to a certain extent by genetics.
Dr. Aaron Carroll: I want to talk about the first half of what you just described first. So when we say that the liver can process drugs at different rates, is it just you have a liver that is more over or underactive in general, or is it literally down to you process certain drugs faster and certain drugs slower, and there's a 1,000 different things going on.
Dr. Todd Skaar: Yeah. No, it's very specific for those specific drugs. There's a handful of different enzymes that specifically metabolize a given drug. So everybody could have a perfectly healthy liver, it's just a little bit different. Just like one person might have blonde hair and another person might have brown hair. One person might be really tall, might be really short. Our livers are a little bit different in that same way. And so in some cases, it's very specific to the specific drug.
Dr. Aaron Carroll: Why evolutionarily would that be? Why did we have that?
Dr. Todd Skaar: These enzymes, through evolution, work designed because we knew in the 20th century, 21st century, we were going to start having drugs to metabolize. I don't think that's why they came up. What they're really for, we think as they were designed to metabolize things that we absorb through stuff that we eat. So it could be different carcinogens, it could be different toxic things, it could be some of them metabolize hormones in our body and their normal processes that our liver uses, just to get rid of these things that we just don't want hanging around in our body forever.
Well, it turns out these drugs that we take, these specific drugs, fit into those same chemical identities. So they look sort of like other compounds that our livers have been developed to get rid of over the years.
Dr. Aaron Carroll: So in general, is it better... Do drugs work better if we metabolize them more slowly or more quickly? How does that play out?
Dr. Todd Skaar: So that depends on the drug and this is where you get into some of those details. So in some cases, the liver just inactivates drugs and excrete some, and you get rid of them, it gets gone out of your body. In other cases, the liver actually activates the drugs. So there are some drugs for example, some of the opioids that themselves are not really very active and they don't do a good job of controlling pain, but the liver can actually metabolize them and act them into a really active compound, which is what actually gives you the pain relief.
And coding is a sort of a classic example of that, where a code in itself is not active, but your liver metabolizes it to morphine. And that is what actually gives you the effect. So it depends on the drug. In some cases, it will mean that you won't respond to the drug and you won't get any beneficial effects. In other cases, it means you're going to build up really high levels of the active drug and you're susceptible to having really bad side effects.
Dr. Aaron Carroll: So this could also... It's not just in how well it works, but this also comes into play with how much harm it's causing you as well and with respect to side effects?
Dr. Todd Skaar: Exactly. Yeah, definitely.
Dr. Aaron Carroll: You also mentioned that this could also have an effect in sort of the targets and how well a drug or not how well a drug would work. How does that come in to play?
Dr. Todd Skaar: Going back to for example, some of the opioids. So we have the targets for those drugs are in our brains for the most part. There are the opioid receptors and there are genetic variants in those receptors that can impact the way the drug actually works on our brains to control pain. And that would be one example of where it actually impacts it.
In other cases, some of our blood pressure medicines target certain receptors that either relax or tighten up our blood vessels. And some of those, there's genetic variance in those. And sometimes the drug binds better or it doesn't bind as strong to those. And that can impact the way we respond to those also.
Dr. Aaron Carroll: What prevents us just from saying, "Well, why don't we just give you the drug and see how it works?" Why does knowing this ahead of time benefit us?
Dr. Todd Skaar: Because in some cases, if we use for example, the toxicity cases, some of the drugs like azathioprine or mercaptopurine that are chemotherapy drugs, have a very, what we call, narrow therapeutic index. So we have to maintain those levels at a very close level within the blood, because if you get too high levels, you can get really sick, you can end up with hospitalization. And in some cases, they could even be lethal if we don't know, because the drug levels in some people can be up 10, 20, 50, or a 100 fold higher than what we really want because they can't eliminate the drugs.
And in other cases, where it's activating it like pain for example, you really don't want to take a drug for a couple of days and then come back and say, "Well, it's not working." In the meantime, you're living through this really horrible pain because the drug isn't working. So getting ahead of the pain control up front makes it much easier to control it as obviously, a better quality of life for those people.
Dr. Aaron Carroll: So it would seem like there's just so many variables at play, so many different potential genes that could affect so many different drugs. For how many drugs, how many different diseases and sort of how many different [inaudible 00:10:03] How many things can we do this on right now?
Dr. Todd Skaar: From a clinical implementation step, which is what we're working on with the Precision Health Initiative here, there's probably a handful, maybe a dozen to two dozen where we could say we really have enough evidence where we can go and say, "In clinical practice, you really could be using it." Probably closer to a dozen. However, if you look at where there's really evidence for a response, but not quite enough evidence, where we should really say you should change somebody's care on that, then it gets up to be much higher.
Right now in the FDA labels, there's over 200 drugs that have some comment in the FDA labels that says there is a genetic component to the response of these drugs. But in some cases, there aren't good alternatives. In some cases, we don't know exactly good enough how to really use that yet, but there is some evidence. So it depends on the degree of evidence.
Dr. Aaron Carroll: So do you need to get a specific genetic test for each specific genetic drug, or is it that you just get your genome and coded, and then you can just go back and check any of these things?
Dr. Todd Skaar: So you could do it both ways. Right now we're focusing on a limited number of genetic tests that are what we would consider clinically actionable. So if your doctor knows what the genetic test results are, they have something they can do to actually change their therapy. We have about a dozen genes that we have on that list.
You could go and sequence your entire genome and pull it out near the information out from there. At this point, that's just a lot more expensive and the informatics tools required to do that make it much more difficult to do that.
Dr. Aaron Carroll: So what are the diseases right now you're focusing on?
Dr. Todd Skaar: There's a couple of them. The first one is cardiology, so patients who have recently got a stint because they had a heart attack or something where they needed a stint, and they get a drug called clopidogrel. The brand name is Plavix. We now have as part of the routine care for those patients, we have a genetic test for, it's called cytochrome P450 2c19, to test to determine whether clopidogrel is the best drug for them or not.
And the nice thing is if it's not, if they can't activate that drug and make it work because of the genetics of their liver, there're other drugs they can take instead. So that's one of the first ones, another one is a genetic test for one of the immune modulator drugs that's used for our solid organ transplant. So kidney transplants, heart transplant, lung transplant. The drug is called tacrolimus, and that has a different genetic test. It's a different enzyme that does it, so we've started testing those for patients who are either donated or actually receiving the kidney transplant.
There's an oncology drug for [inaudible 00:13:03] and 5-fluorouracil. There's a gene that is responsible for primarily eliminating that drug, and if you don't have that enzyme because of genetic variance, you get really high levels and really bad toxicities due to that. So those are some of the first ones. And then we're rolling out into other ones.
Dr. Aaron Carroll: How much did these genetic tests cost?
Dr. Todd Skaar: Like any sort of test on the market like that, it can range from around a couple of $100 up to... Depending on if you do a lot of different genes, it would be more than that. It could be up to a $1,000 or so, but generally they're in the $200 to $300 per patient. And that can actually give you a test for multiple different drugs because we now run those typically as a panel of genetic tests, rather than just individual ones.
Dr. Aaron Carroll: Well, that was my next question, is are there sort of just some general pathways that account for a decent number of drugs, or is it really very individual to every drug?
Dr. Todd Skaar: No. And that's one of the nice things about this, is if you test for, for example, the clopidogrel test I was just talking about, the enzyme that metabolizes that is also the same one that metabolizes some of the antidepressants and some of the antifungal drugs. And so in some cases, you can do one test and then as long as we keep it in their medical records, or the patient has it, if they're a year or two or five years down the road, they may get a different drug, and that same test can actually be used for multiple different drugs.
So we have about a dozen genes that are the ones that we're testing for that test for a variety of... Another dozen or two dozen drugs, but some of them can be used for multiple different drugs. And that's one of the nice things about it.
Dr. Aaron Carroll: So how commonly is this done now? Is this the kind of thing that we're still saying it's experimental or trying it out with different patients, or are there some drugs now where it's like, "Oh well, if you're even thinking of using this drug, you get the genetic test first?"
Dr. Todd Skaar: Both, but there are some... The ones we're really focused on... Well, there's two parts we're focused on. One is the ones that you really should be using this, and the cardiology example I just gave is one of them. There are some FDA labels that say, "You should not use this drug unless you have had this genetic test upfront." Like carbamazepine with patients that have Asian ancestry and some things like that. Some of the new neurology drugs that have come out are like that, and you really need to use them.
And then there're other ones where there's a lot of research evidence for it. We know how they work, but there isn't quite enough to cross that line where we really should say, "You really should be doing this test." And so that's sort of the basis of a couple of big clinical trials that we're starting. We're really going to do that last step to say, "If you use the test, are your outcomes better than somebody who did not get the test?"
Dr. Aaron Carroll: So can you walk us through some of those studies, how do those work?
Dr. Todd Skaar: Sure. One study now is focused on pain control in patients that are having surgery for like a hip and knee replacements, that they commonly get opioids for pain control after their surgery. These are patients that wouldn't normally get the genetic test.
And so what we're doing is enrolling them, consenting them, patients who are interested along with their doctors, and then half of them will get randomized to get the genetic test. And the other half will get just therapy the way they normally would have gotten it if they weren't part of the trial. And then through patient reported outcomes, we're asking them how their pain control was and how much opioids or how much drugs they needed to actually control that pain. And it will look at outcomes like 10 days later in a month, in three months. And then even long-term, things like did they end up having to use opioids for over a long period of time? That's sort of beyond the scope of that trial. And other ones are used at different end points, like antidepressants is another one.
So we're doing that, looking at depression control. Another study is chronic pain control. So that's sort of from a pharmacogenomic standpoint, how we really test it and then look at the end. Did it really improve the health care of that patient?
Dr. Aaron Carroll: Do you start with the drug and then look for a gene, or do you start with the gene and then look for a drug? Or is it a combination of the two?
Dr. Todd Skaar: Usually it's starting with the drug and looking for the gene. So there's a couple of ways to typically do it. So the field originally started back in the 50s and 60s where somebody, a patient would get a drug and they would have just a really prolonged or exaggerated response to it. And then you would say, "Well, what's different about that patient than the rest of the population?" We still do that some today. So we just published a report where a patient that got a couple of doses of capecitabine ended up with such bad toxicity. She ended up in the hospital for three weeks.
And so we went in and said, "What is it that's different about that patient? What sort of rare genetics does that patient have that's unusual?" And we figured it out and it turned out it was one of the enzymes that metabolizes that. Usually we start with the drug and look in some cases, individual, really what we call extreme responders like that. In other cases, we might take like a clinical trial and then say, "Okay, let's split them," and say, "Look at the group that had the best response." Maybe it was a blood pressure medication and some that had a really good control of their blood pressure, and other ones where it didn't really do much.
And then we'll look at in some cases, their whole genome or millions of these genetic variants across their whole genome and try and say, "What is it that's different between those groups of patients?" And then eventually, focus in on the genes. In some cases, we know something about the way the drug is metabolized, or we know the targets. So we may zoom in real early on, on some of those genes and say, "Are they responsible for it?" Or sometimes we just look in an unbiased way at the entire genome.
Dr. Aaron Carroll: And is it usually one gene, one drug, or is it sometimes multiple genes per drug interacting in a variety of different ways?
Dr. Todd Skaar: Most of the tests that we use now are a single gene for each drug, but there are exceptions to that. Some of the antidepressants are exceptions. A couple of the cancer drugs are exceptions to those, but in general, it's usually one, but that's as of what we know today. As we do more of this research and we're going to understand, I think that there's multiple genes that are involved in it and genetic variance across multiple different genes that really impacted.
And as we go, I think we will have these multi gene panels that hopefully will do even a better job of predicting the response, because these still aren't perfect. There's still a lot of variability that we don't understand yet.
Dr. Aaron Carroll: Well, that was actually my next question. So I'm always impressed that when we do drug trials or when patients are wondering how well does this drug work? I think the public sometimes sees this in a very binary way, that the drug works or the drug does not work. But in reality, it's hugely different responses between patients. It's just your average is slightly better on one... If you take the drug than not. Do you think that that huge variation... How much of that do you think is genetics versus other things?
Dr. Todd Skaar: Yeah, I wish I knew that for sure. That's a really good question, and I think that depends on the drug. In some cases, in some of these big genetic tests or genetic studies that we've done, there are genes that have a really big impact and it has a lot to do with it. In other cases, we've done it and there's just nothing really that comes out and we can't really find real obvious hits. And in some cases, the toxicities are easier to find than the efficacy ones.
But it's hard to say, there's a lot of... We're talking about a really complicated system from the time... Especially in people that are in their 40s, 50s, 60s or older, where they've been exposed to all kinds of different environmental things, their diets are different, their genetics are different. There's just so many things that complicate it. So I don't know, in some cases, it's a lot of genetics, in some cases it's probably very little.
Dr. Aaron Carroll: Could you just talk a little bit more about the other things which you think might be at play if it's not genetics? I know you mentioned diet and environment, but how much do you think each of these contribute? And I know some of this is your best guess, a lot of this is very still not studied, detailed, but just sort of qualitatively, what do you think the other factors are?
Dr. Todd Skaar: One that's important I think is what other drugs they're taking? So that, we would consider an environmental impact. In some cases, nutrition can have an impact, drugs like Warfarin, Coumadin, the amount of vitamin K that people are taking in their diets can impact that. Patients, in some cases, their physical activity I think might impact it. And their body weight, whether they're lean versus obese, and things like the pregnancy can impact temporarily, the way drugs act. So there're impacts, there're things there.
Probably the biggest, or one of the biggest things that impacts it is the compliance with the regimen. So if you're supposed to take it twice a day and the patients forget half of the time, and they don't take it, or they don't get the drug refills, or whatever. So I think all of those things together have a big impact, and genetics plays a part of it, but only a part of it.
Dr. Aaron Carroll: So I know we're doing a lot of work locally, but you're part of a large trial called Ignite. Can I get you to talk about that a little bit?
Dr. Todd Skaar: Sure. And this was an NIH funded network that was started now about seven or eight years ago, where the National Human Genome Research Institute got some experts together a year or so before that and said, "We really are now after we sequenced the human genome, we are getting really good at understanding the genetics, and had a lot of genetic information, but people weren't really using it to the extent that we thought it might be possible."
And so they set up a network that was originally funded six different groups across the United States. And they really said, "Go out and figure out what the barriers are to implementing this genetic testing. We understand you're going to run into a bunch of problems and barriers, but go out and try it and break down some of those barriers and overcome some of those problems."
And so everybody had different, slightly different trials they were running. Ours was a pharmacogenetics trial where we focused on doing... As I mentioned earlier, where we randomized people to either get their drugs the way they would normally get it, or we genotype them and provided that information to the doctors. And then we're looking at outcomes, but we haven't completed the outcomes analysis yet. In the next few months, we should have that. Looking at both, did we reduce the number of adverse events and the number of side effects, the number of re-hospitalizations and these things that are oftentimes come along with some drug therapies?
So number one, did we do that? And then did we also really make it cheaper so that we reduce the healthcare utilization through number of visits and that sort of thing. So that was our study, we're in the middle of doing that. And then each other site had their own study that they were running also. And that was the Ignite one, the first part of that has now been completed. The funding is done, everybody just wrapped up their studies.
And now we're starting with the Ignite two, which we've been funded now about two years. And that's the trials that I mentioned, like the surgery, the opioid response and surgery, and some of those trials, as well as one other one, which we've just started rolling last week... I think two weeks ago in a trial that's called Guard. And what that is, is focused on genetic testing that we think will help patients do a better job of controlling their blood pressure. We've known that patients of African descent have a higher risk. If they have a high blood pressure, they have a higher risk of progressing to chronic kidney disease, than do people with other ancestries.
And now, because of a variety of genetic analysis, we understand that that is due to... About half of that risk is due to a genetic variant in a gene called [inaudible 00:25:59] and one of the other sites in the previous study had shown that if you do the test and you relay that information back to the patients and their providers, their doctors, they understand they're at high risk and they do a better job of controlling their blood pressure.
And so this is a way to do a genetic test, return the results to them with hopes that they do that, and then ultimately have a less risk of going on to chronic kidney disease. And so this will be in African-American patients with hypertension, and we will be enrolling over a 1,000 people from Indiana in that trial.
Dr. Aaron Carroll: So there's a question, unfortunately, I wish we didn't have to ask, but we've asked guests recently. How has the pandemic affected this kind of work?
Dr. Todd Skaar: So that trial was supposed to start at about four months ago because we were just getting ready about the time the pandemic started. And so we really had to stop for a few months. We couldn't start enrolling that. So that's now as we're really... We've got all our mechanisms in place to prevent any potential transmission of the virus or anything. So we've now got that, so we're now starting to do it.
It's a little more complicated because the physician visits are down and that's where we're recruiting some of the patients. There may be some patients that are less likely to come in. So it's slowed it down, but we're really focused on getting it back up and going. And we're excited because we started this trial a week or two ago, and we've already enrolled, I think about 10 patients in it. So it slowed it down, but it didn't stop us.
Dr. Aaron Carroll: Do you think that we're going to just keep heading in this direction, that more and more drugs are going to have genetic tests and eventually it'll just be all drugs? We just check your genes and we say, "These are the drugs you should take. These are the drugs that won't work?"
Dr. Todd Skaar: I think there will be more and more. I can't guarantee all of them will have it. I would imagine there is some genetic component to the response to every drug. I think the question is whether that genetic component is big enough to make it clinically actionable or not and whether you would really change the therapies or not. Eventually, we will probably all have our whole genome sequenced, and we will... Or at least anybody who wants it and there'll be a lot of understanding of that. And we probably will be able to use it much more eventually.
I wish I knew the timeframe on that. That's hard to predict, but it's coming fast. If you look at the progress that's been made in genomics over the last decade, it's going at light speed. So I think we'll see a lot more of it.
Dr. Aaron Carroll: When people are getting those genetic tests, are they blood tests or do you get the sample some other way?
Dr. Todd Skaar: The easiest way from a lab standpoint is doing a blood test. So it's just a small blood sample, but we can do it from saliva. So we can just have people spit in a little cup and then we process out of that, so that works too. Those are the two main ways, sometimes just a swab, or you can just swab the inside of your mouth and get some cheek cells and do it that way too. But most of it is [inaudible 00:28:55].
Dr. Aaron Carroll: So when you develop one of these genetic tests, is it something other labs can just do? Do they have to buy the tests from you, or is it some set up where you're like, "Oh, you just check X, Y, and Z?" How do you distribute these tests to other labs?"
Dr. Todd Skaar: Usually, there's a variety of different labs and we're all basically using commercial reagents that we're just buying and setting up, and going through the clinical validation of it to make sure they're right. But for the most part, these tests have been around for a while through all the research and stuff, so they're pretty much publicly available, and different labs just buy the reagents off the shelf and run them.
Dr. Aaron Carroll: We've talked to a number of scientists who all work in the Precision Health Initiative. This one is one of the first ones where I'm like, "I totally get, this is Precision Health. This is literally it." So are you fitting into sort of all the other trials? Is there like a pharmacogenomics component of everything?
Dr. Todd Skaar: Not necessarily all of them, and because part of it is at this point, we don't know how to actually use them. Some of the other ones, it's just been hard to identify the genetic component to it. In some cases, it might be the environmental impact is so big that it's hard to weed out the genetic component. And diabetes might be one of those, there's a lot of environmental things that impact diabetes so the genetics may be harder to go.
But we're trying, so as much as we can, I think in most of the trials now, most of the investigators are collecting DNA. So eventually, hopefully we can try do that.
Dr. Aaron Carroll: How do you return the results to patients? What do they do with them?
Dr. Todd Skaar: One of the interesting things that we're doing is returning the genetic results directly to the patient. And there's been some direct to consumer testing where the consumer gets it back. And what we're trying to do is understand how to best do that because if our patients are going to Eskenazi or IU Health, or one of the healthcare systems that we're working on, and the genetic test results are in the medical records, that's fine. But if the patient is on vacation in California or Alaska, or somewhere else, and they have an accident or something, we're trying to get the genetic test results in the patient's hands too so they can actually use it wherever they are.
And so that's one of the forefronts that we're really trying to understand better, is how do we best safely and effectively return these results to patients, and educate them and let them know it's like, "Okay, here's when you need to show this to the doctor, here's when you shouldn't. But don't change any of your strategies without talking to your doctor, because they might look at things and misinterpret it." And for those of us that think about genetics day at night, it might be pretty obvious, but the most of the patients don't, and they just want to know what should they do?
And we want to make sure as we're doing this, we're making the testing usable in as many cases as possible, but doing it safely and effectively, so they don't do something they shouldn't do by mistake with it.
Dr. Aaron Carroll: Well, we'd love to have you back when more information is out. Thanks so much for joining us.
Dr. Todd Skaar: Thank you.
Dr. Aaron Carroll: Again, this podcast is sponsored by Indiana University School of Medicine, whose mission is to advance health in the state of Indiana and beyond, by promoting innovation and excellence in education, research, and patient care.